KR101356454B1 - Method for preparing unsaturated aldehyde compound - Google Patents

Abstract

The present invention relates to a method for producing an unsaturated aldehyde compound, comprising the step of reacting propazyl alcohol in the presence of a sulfonic acid compound and a dichloroethane solvent, the reaction step is very simple compared to the conventional, there is no by-product, yield And a method capable of producing unsaturated aldehyde compounds with high purity.

Description

Method for preparing unsaturated aldehyde compound {METHOD OF PREPARING UNSATURATED ALDEHYDE COMPOUND}

The present invention relates to a process for preparing unsaturated aldehyde compounds from propazyl alcohol.

Among unsaturated aldehyde compounds, α, β-unsaturated aldehyde compounds are not only basic skeletons of natural products showing physiological activity, but are also recognized as very important intermediates in organic synthesis. In particular, it is a core skeleton structure that is used as a precursor of various organic synthesis reactions for synthesizing a compound of a complex structure, the development of its synthesis method is an important field.

Aldol reaction, Knoevenagel-type condensation reaction, Wittig reaction, and Horner-Wadsworth-Emmons reaction are known to synthesize α, β-unsaturated aldehyde compounds, but various functional groups exist because they are economical and are carried out under strong base conditions. In the case of a substrate that has a limited disadvantage.

Recently, in the Meyer-Schuster repositioning reaction for synthesizing an α, β-unsaturated aldehyde compound using a repositioning reaction of propazyl alcohol, a method of using gold as a catalyst as a catalyst has been attracting attention [ Org . Biomol . Chem . 2009 , 7 , 4149]

However, the Meyer-Schuster relocation reaction using the gold catalyst has a high price, which makes industrial production difficult, and in some cases, the catalyst is toxic.

In addition, a method of preparing an aldehyde-based compound from a pyridine derivative using p-toluene sulfonic acid instead of a metal catalyst has been proposed [Korean Patent No. 569,829], but the target product is 3,5-difluoropyridine-4-carb. It is an aldehyde and has a disadvantage in that the reaction time is long because a four-step reaction is performed.

The present invention is a simple reaction in the Meyer-Schuster repositioning reaction of propazyl alcohol, there is no by-product, high yield and purity, economically advantageous unsaturated aldehyde compound, especially among α, β-unsaturated aldehyde compound The purpose is to provide a method of manufacturing.

In order to achieve the above object, the present invention comprises the step of reacting the propazyl alcohol of the formula (1) in the presence of a sulfonic acid compound and a dichloroethane solvent to prepare an α, β-unsaturated aldehyde compound of the formula (2) It provides a method for producing an unsaturated aldehyde compound.

(Wherein R ₁ and R ₂ are each independently hydrogen, a halogen element, a substituted or unsubstituted aryl group having 3 to 20 carbon atoms, a substituted or unsubstituted alkyl group having 1 to 10 carbon atoms)

The sulfonic acid compound may be at least one selected from the group consisting of methanesulfonic acid, phenylsulfonic acid and para-toluenesulfonic acid.

The sulfonic acid compound may be used in an amount of 0.1 to 0.5 equivalents based on 1 equivalent of the propazyl alcohol of Formula 1.

The reaction may be carried out at a temperature of 60 to 90 ℃.

Preferably, R ₁ and R ₂ are each independently hydrogen; Halogen element; Substituted or unsubstituted phenyl group, benzyl group, biphenyl group or naphthyl group; Linear or crushed alkyl groups having 1 to 9 carbon atoms; Or an aliphatic cyclic alkyl group having 3 to 8 carbon atoms.

More preferably, the phenyl group, benzyl group, biphenyl group or naphthyl group may be substituted with an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a hydroxy group, an acetyl group, an amide group or a nitrile group. .

,

,

,

,

,

또는

일 수 있다.
The unsaturated aldehyde compound is

,

,

,

,

,

or

Lt; / RTI >

Unsaturated aldehyde compounds according to the present invention has the advantage of a very simple reaction step, no by-products, high yield and high purity compared to the prior art.

In addition, the unsaturated aldehyde compound according to the present invention has the advantage that the economic efficiency is improved by using an inexpensive catalyst compared to the conventional.

In this way, the prepared unsaturated aldehyde compounds, in particular α, β-unsaturated aldehyde compounds can be used not only as a basic skeleton of a natural product having physiological activity, but also can be used for new drug development and various drug development.

The present invention relates to a process for preparing unsaturated aldehyde compounds from propazyl alcohol.

Hereinafter, the present invention will be described in detail.

The method for preparing an unsaturated aldehyde compound according to the present invention comprises the step of reacting the propazyl alcohol of the formula (1) in the presence of a sulfonic acid compound and a dichloroethane solvent to prepare an α, β-unsaturated aldehyde compound of the formula (2) It provides a method for producing an unsaturated aldehyde compound.

(Wherein R ₁ and R ₂ are each independently hydrogen, a halogen element, a substituted or unsubstituted aryl group having 3 to 20 carbon atoms, a substituted or unsubstituted alkyl group having 1 to 10 carbon atoms)

Preferably, R ₁ and R ₂ are each independently hydrogen; Halogen element; Substituted or unsubstituted phenyl group, benzyl group, biphenyl group or naphthyl group; Linear or crushed alkyl groups having 1 to 9 carbon atoms; Or an aliphatic cyclic alkyl group having 3 to 8 carbon atoms.

More preferably, the phenyl group, benzyl group, biphenyl group or naphthyl group may be substituted with an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a hydroxy group, an acetyl group, an amide group or a nitrile group. .

,

,

,

,

,

또는

일 수 있다.
The unsaturated aldehyde compound is

,

,

,

,

,

or

Lt; / RTI >

The preparation method according to the present invention prepares the unsaturated aldehyde compound of the formula (2) by the Meyer-Schuster relocation reaction of the propazyl alcohol of the formula (1). At this time, a sulfonic acid catalyst is used as Brønsted acid, and dichloroethane, which has a relatively high polarity, is used as a solvent.

Usually, the solvent dissolves the reactants and does not inhibit the reaction. However, in the present invention, dichloroethane is selected as a solvent having a high reaction rate and excellent yield.

In this case, solvents generally used in the art, specifically, from the group consisting of dichloromethane, dichloroethane, toluene, acetonitrile, nitromethane, tetrahydrofuran, N, N-dimethylformamide, and N, N-dimethylacetamide One or more selected species may be used in combination. It is preferable to mix the said common solvent below 50 weight part with respect to 100 weight part of dichloroethane at the time of mixing use.

The sulfonic acid catalyst may be at least one selected from the group consisting of methanesulfonic acid, phenylsulfonic acid and para-toluenesulfonic acid. Preference is given to using para-toluenesulfonic acid with a high double reaction rate and good yield.

The sulfonic acid catalyst may be used in an amount of 0.1 to 0.5 equivalents, preferably 0.1 to 0.2 equivalents, based on 1 equivalent of the propazyl alcohol of Formula 1. If the amount is less than 0.1 equivalent, the amount may be insignificant so that the reaction yield may be low, and when the amount exceeds 0.5 equivalent, many by-products may occur.

The reaction may vary in temperature depending on the type of reactant, specifically, it may be carried out at 60 to 90 ℃, preferably 40 to 60 ℃. Moreover, it is preferable to adjust reaction time suitably according to the kind of reaction material, the kind of catalyst, the usage-amount of reaction solvent, a reaction apparatus, reaction temperature, etc.

The reaction can be confirmed the completion of the reaction through a conventional method such as TLC, when the reaction is completed can be carried out a conventional separation and purification.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the present invention. Such variations and modifications are intended to be within the scope of the appended claims.

Example  One: Cinnamic Aldehyde

, 55.7mg, 수율: 84%, 순도: 99%)을 얻었다.Para-toluenesulfonic acid (28.53mg, 0.15mmol) was added to the test tube, dichloroethane (DCE, 3mL) was added, and then 1-ethynyl-2-propane-1-ol (66.08mg, 0.5mmol) was added. Added and stirred at 60 ° C. After 1 hour, when the reaction is completed, the solvent is removed and separated by tube chromatography.

, 55.7 mg, yield: 84%, purity: 99%).

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.70 (d, J = 7.7 Hz, 1H), 7.58-7.55 (m, 1H, H), 7.50 (d, J = 16.0 Hz, 1H), 7.45-7.43 ( m, 4H,), 6.72 (dd, J = 7.7 Hz, J = 16.0 Hz, 1H).

Example  2: 4- methyl - Cinnamic Aldehyde

, 70.3mg, 수율: 96%, 순도: 99%)을 얻었다.Para-toluenesulfonic acid (28.53mg, 0.15mmol) was added to the test tube, dichloroethane (DCE, 3mL) was added, and then 1- (4-methylphenyl) -2-propane-1-ol (73.09mg, 0.5 mmol) was added and stirred at 60 ° C. After 2 hours, when the reaction was terminated, the solvent was removed, and then separated by column chromatography to 4-methyl-cinnamaldehyde (

, 70.3 mg, yield: 96%, purity: 99%).

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.68 (d, J = 7.7 Hz, 1H), 7.49-7.43 (m, 3H), 7.26-7.23 (m, 2H), 6.69 (dd, J = 7.7 Hz, J = 15.9 Hz, 1H), 2.40 (s, 3H).

Example  3: 4- Methoxy - Cinnamic Aldehyde

, 69.3mg, 수율: 82%, 순도: 99%)을 얻었다.Para-toluenesulfonic acid (28.53 mg, 0.15 mmol) was added to the test tube, dichloroethane (DCE, 3 mL) was added, followed by 1- (4-methoxyphenyl) -2-propane-1-ol (84.58 mg). , 0.5 mmol) was added and stirred at 60 ° C. After 2 hours, the reaction was terminated, the solvent was removed and separated by tube chromatography to 4-methoxy-cinnamaldehyde (

, 69.3 mg, yield: 82%, purity: 99%).

¹ H NMR (400 MHz, CDCl _{3 ,} ) δ 9.66 (d, J = 7.7 Hz, 1H), 7.53 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 15.9 Hz, 1H), 6.95 ( d, J = 8.7 Hz, 2H), 6.61 (dd, J = 7.7 Hz, J = 15.9 Hz, 1H), 3.86 (s, 3H).

Example  4: 2- Bromo - Cinnamic Aldehyde

, 68.8mg, 수율: 65%, 순도: 99%)을 얻었다.Add para-toluenesulfonic acid (28.53mg, 0.15mmol) to the test tube, add dichloroethane (DCE, 3mL), and then add 1- (2-bromophenyl) -2-propane-1-ol (105.53mg). , 0.5 mmol) was added and stirred at 60 ° C. After 2 hours, the reaction was terminated, the solvent was removed and separated by column chromatography to 2-bromo-cinnamaldehyde (

, 68.8 mg, yield: 65%, purity: 99%).

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.77 (d, J = 7.7 Hz, 1H), 7.90 (d, J = 15.9 Hz, 1H), 7.67-7.64 (m, 2H), 7.37-7.30 (m, 1H), 7.28-7.26 (m, 1H), 6.67 (dd, J = 7.7 Hz, J = 15.9 Hz, 1H).

Example  5: 4- Chloro - Cinnamic Aldehyde

, , 68.8mg, 수율: 83%, 순도: 99%)을 얻었다.Para-toluenesulfonic acid (28.53mg, 0.15mmol) was added to the test tube, dichloroethane (DCE, 3mL) was added, and then 1- (4-chlorophenyl) -2-propane-1-ol (83.30mg, 0.5 mmol) was added and stirred at 60 ° C. After 1 hour, the reaction was terminated, the solvent was removed and separated by column chromatography to 4-chloro-cinnamaldehyde (

,, 68.8 mg, yield: 83%, purity: 99%) was obtained.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.70 (d, J = 7.7 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 15.9 Hz, 1H), 7.40 (d , J = 8.7 Hz, 2H), 6.68 (dd, J = 7.7 Hz, J = 15.9 Hz, 1H).

Example  6: 1,1,3- Triphenyl - Propenone

, , 118.1mg, 수율: 83%, 순도: 99%)을 얻었다.Para-toluenesulfonic acid (28.53mg, 0.15mmol) was added to the test tube, dichloroethane (DCE, 3mL) was added, and then 1,1,3-triphenylpropazyl alcohol (142.2mg, 0.5mmol) was added. It stirred at 60 degreeC. After 6 hours, when the reaction was terminated, the solvent was removed, and then separated by tube chromatography to obtain 1,1,3-triphenyl-propenone (

,, 118.1 mg, yield: 83%, purity: 99%) was obtained.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.91 (d, J = 7.1 Hz, 2H), 7.46-7.51 (m, 1H), 7.35-7.40 (m, 7H), 7.25-7.28 (m, 2H), 7.16-7.21 (m, 2 H), 7.12 (s, 1 H).

Example 7: Crotonaldehyde

, 63.3mg, 수율: 85%, 순도: 99%)을 얻었다.Para-toluenesulfonic acid (28.53 mg, 0.15 mmol) was added to the test tube, dichloroethane (DCE, 3 mL) was added, followed by 2-phenyl-3-butyn-2-ol (73.08 mg, 0.5 mmol). It stirred at 60 degreeC. After 6 hours, when the reaction is terminated, the solvent is removed, and then separated by tube chromatography to obtain crotonaldehyde (

, 63.3 mg, yield: 85%, purity: 99%).

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.06 (d, J = 7.1 Hz, 1H), 6.36 (d, J = 7.1 Hz, 1H), 5.95 (t, J = 6.0 Hz, 1H), 2.20 (s , 3H), 2.15-2.11 (s, 4H), 1.62-1.52 (m, 4H).

Claims (7)

In the presence of a sulfonic acid compound and a dichloroethane solvent, reacting the propazyl alcohol of Formula 1 at a temperature of 60 to 90 ° C. to produce an α, β-unsaturated aldehyde compound of Formula 2, wherein the unsaturated aldehyde compound is prepared. Manufacturing Method:

(Wherein R ₁ and R ₂ are each independently hydrogen, a halogen element, a substituted or unsubstituted aryl group having 3 to 20 carbon atoms, a substituted or unsubstituted alkyl group having 1 to 10 carbon atoms)
The method of claim 1, wherein the sulfonic acid compound is at least one selected from the group consisting of methanesulfonic acid, phenylsulfonic acid and para-toluenesulfonic acid.
The method of claim 2, wherein the sulfonic acid compound is used in an amount of 0.1 to 0.5 equivalents based on 1 equivalent of propazyl alcohol of Formula 1.
delete The method according to claim 1, wherein R ₁ and R ₂ are each independently hydrogen; Halogen element; Substituted or unsubstituted phenyl group, benzyl group, biphenyl group or naphthyl group; Linear or crushed alkyl groups having 1 to 9 carbon atoms; Or an aliphatic cyclic alkyl group having 3 to 8 carbon atoms.
The method of claim 5, wherein the phenyl group, benzyl group, biphenyl group or naphthyl group is characterized in that the alkyl group having 1 to 5 carbon atoms, the alkoxy group having 1 to 5 carbon atoms, hydroxy group, acetyl group, amide group or nitrile group is substituted Method of producing an unsaturated aldehyde compound.
The method of claim 6, wherein the unsaturated aldehyde compound

,

,

,

,

,

or

Method for producing an unsaturated aldehyde compound, characterized in that.